Structure-function relationship of CAP-Gly domains

Nat Struct Mol Biol. 2007 Oct;14(10):959-67. doi: 10.1038/nsmb1291. Epub 2007 Sep 9.


In all eukaryotes, CAP-Gly proteins control important cellular processes. The molecular mechanisms underlying the functions of CAP-Gly domains, however, are still poorly understood. Here we use the complex formed between the CAP-Gly domain of p150(glued) and the C-terminal zinc knuckle of CLIP170 as a model system to explore the structure-function relationship of CAP-Gly-mediated protein interactions. We demonstrate that the conserved GKNDG motif of CAP-Gly domains is responsible for targeting to the C-terminal EEY/F sequence motifs of CLIP170, EB proteins and microtubules. The CAP-Gly-EEY/F interaction is essential for the recruitment of the dynactin complex by CLIP170 and for activation of CLIP170. Our findings define the molecular basis of CAP-Gly domain function, including the tubulin detyrosination-tyrosination cycle. They further establish fundamental roles for the interaction between CAP-Gly proteins and C-terminal EEY/F sequence motifs in regulating complex and dynamic cellular processes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Crystallography, X-Ray
  • Dynactin Complex
  • Dyneins / chemistry
  • Dyneins / genetics
  • Dyneins / metabolism
  • Humans
  • Microtubule-Associated Proteins* / chemistry
  • Microtubule-Associated Proteins* / genetics
  • Microtubule-Associated Proteins* / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Neoplasm Proteins* / chemistry
  • Neoplasm Proteins* / genetics
  • Neoplasm Proteins* / metabolism
  • Protein Binding
  • Protein Conformation*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sequence Alignment
  • Structure-Activity Relationship*


  • DCTN1 protein, human
  • Dynactin Complex
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Recombinant Fusion Proteins
  • cytoplasmic linker protein 170
  • Dyneins

Associated data

  • PDB/2PZO